selected topics in the neuropathology of epilepsy ty abel m.d., ph.d october 9, 2013
TRANSCRIPT
Epilepsy
• "an episodic disorder of the nervous system arising from the excessively synchronous and sustained discharge of a group of nerve cells"
Hughlings Jackson, 1873
Epilepsy-Classification
• Primary: epilepsy that occurs in the absence of other syndromes or disorders. Presumed to have a genetic basis e.g., Benign Neonatal Familial Convulsions, Juvenile Myoclonic Epilepsy
• Secondary: a primary pathology exists independent from the epilepsy e.g., trauma, infection, neoplasm etc
Secondary Epilepsy
• Trauma• Vascular malformations• Cerebral malformations• Rasmussen's Syndrome• Mesial Temporal Sclerosis• Neoplasms
Epilepsy-General Concepts
• Cortical lesions (often temporal) more likely to produce seizures than deep-seated lesions
• If cause is neoplasm, most likely a well-differentiated one
• Radiographic features can aid in the differential diagnosis
• e.g., Focal vs Diffuse
Trauma
• Incidence of epilepsy > with penetrating injuries
• Incidence higher with injury to parietal, motor areas
• Disrupted function due to scar? Blood or blood products in neuropil?
Cavernous Angioma
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Arteriovenous Malformation
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Arteriovenous Malformation
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Sturge-Weber Syndrome• Vascular malformations of the face, eye and brain• Proliferation of leptomeningeal vessels and
laminar cortical calcification• Associated with ipsilateral port-wine stain in
distribution of facial nerve, glaucoma, cerebral atrophy, mental retardation and seizures
• Considered a non-heriditary, developmental malformation cause by somatic mutation in the GNAQ gene.
Sturge-Weber Disease
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Sturge-Weber syndrome
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Cortical Dysplasia
• Cause of chronic seizures in both children and adults
• Thickened cortex and blurred gray-white junction sometimes seen radiographically
• Microscopic: effacement of laminar cortical architecture with extremely large neurons, astrocytes and intermediate ballooned forms
Cortical Dysplasia
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Cortical Dysplasia
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Hemimegalencephaly
• Enlargement of one cerebral hemisphere associated with intractable seizures
• May lead to hemispherectomy• Pathologically, can be associated with diffuse
form of cortical dysplasia, gyral malformations and heterotopias
Hemimegalencephaly
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Rasmussen's Syndrome
• Abrupt childhood onset of seizures with progressive unilateral neurological deficit
• Refractory to anticonvulsants• Etiology unknown-viral?, autoimmune?• Inflammatory process restricted to one
hemisphere• Atrophy, leptomeningeal lymphocytes,
perivascular cuffing, microglial nodules, neuronophagia
Mesial Temporal Sclerosis
• Complex partial seizures• Cause or effect of seizures or both?• Association with prolonged initial seizure in
childhood or recurrent febrile convulsions• Loss of neurons in Ammon's horn, esp. CA1• Dentate granule cell dispersion• Chaslin's subpial gliosis
Hypothalamic Hamartoma
• Gelastic seizures• Precocious puberty• Other endocrine abnormality (e.g.,
acromegaly)
Neoplasms
• Pilocytic Astrocytoma• Pleomorphic Xanthroastrocytoma (PXA)• Ganglion Cell Tumors• Dysembryoplastic Neuroepithelial Tumor
Low-grade Neoplasms-Radiographic features
Ganglioglioma
Other features: superficial location, skull erosion and calcification
Pilocytic Astrocytoma
Burger et al., Surgical Pathology of the Nervous System and its Coverings, 4th Ed, 2002
Juvenile Pilocytic Astrocytoma• Most common childhood glioma• 10% of cerebral and 85% of cerebellar astrocytomas • Classic Radiologic Features• Classic Histology albeit diverse “looks”• Classic Association with NF1• New Association with alterations in BRAF
Peter Burger: Surgical Pathology of the Nervous System and its Coverings
EGF/PDGF
P P
GRB2 GEF
ras-GDP ras-GTPRaf
MEK 1/2
P
P
Erk 1/2PP
EtsElk-1c-fosc/n-mycstat 1/3
cytoplasmnucleus
MEK 1/2
Erk 1/2
plasma membrane
GAP Neurofibromin
Pilocytic Astrocytoma and the Ras Pathway
RAF fusion protein results in constitutively active pathway in sporadic PA
Pilomyxoid: Summary
• No pathognomonic clinical or radiologic characteristics (age?)
• Perivascular tumor cells, myxoid change, cellular monomorphism
• Should be the predominant pattern• Propensity for recurrence, leptomeningeal
spread.
Case study: 12-year-old female
• “Syncopal” episodes for last 9 months• Observed to have seizure in school• CT scan was obtained on the outside
– Outside CT shows heterogeneous, solid and cystic, left occipital lobe mass
• Patient underwent craniotomy on 11/15/2005
Follow-up
• Resolution of seizures• Resolution of post-op surgical changes on
surveillance MRI• Last seen in clinic on 11/14/2012, without
deficits.